Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, today announced that it has released results from a Phase I study of the investigational inhibitor of apoptosis protein (IAP) antagonist APG-1387 in Chinese patients with chronic hepatitis B (CHB), in an oral presentation at the 73rd American Association for the Study of Liver Diseases Annual Meeting (AASLD 2022). This is the world’s first clinical study reporting favorable safety and preliminary efficacy of an IAP antagonist for the treatment of patients with CHB.
Ascentage Pharma Logo (PRNewsfoto/Ascentage Pharma)
Data from this clinical study suggest that APG-1387 has anti-hepatitis B virus (HBV) activity at doses of 12 mg and 30 mg, and synergistic effects when combined with sequential nucleos(t)ide analogue (NA) treatment. These data provide additional rationale for the continued development of APG-1387 in combination with other agents for the functional cure of CHB.
HBV infection is a global public health threat. The World Health Organization (WHO) estimates that approximately 300 million people worldwide are living with hepatitis B and 1.1 million deaths occur annually due to hepatitis B, hepatitis C, and their effects including liver cancer, cirrhosis, and other conditions caused by chronic viral hepatitis1. In China, the surface antigen of the hepatitis B virus (HBsAg) is present in 5%-6% of the population, and there are approximately 70 million patients with chronic HBV infections the country, of whom 20-30 million have CHB2. A total of 77% of liver cirrhosis cases and 84% of all primary hepatocellular carcinoma cases are associated with HBV infections3. Current guidelines recommend entecavir, tenofovir, tenofovir alafenamide, and long-acting interferon as standard anti-HBV treatments. However, only a small percentage of the patients who receive long-term treatment with these therapies can achieve HBsAg negativity and continued immune response after treatment. Majority of the patients require prolonged or even lifetime treatment, thus presenting an enormous unmet medical need for safe and effective therapies that can minimize the risk of disease progression and achieve functional cure with a relatively short duration of treatment.
Discovered and developed by Ascentage Pharma with global intellectual property rights, APG-1387 is a potent and highly selective next-generation IAP antagonist that has already shown anti-HBV potential in preclinical studies. Currently, the drug candidate is being evaluated in a Phase II study for the treatment of patients with CHB in China. APG-1387 can induce apoptosis (programmed death in diseased cells) and confer immune modulation in HBV-infected liver cells, and has the potential as a novel therapeutic for the functional cure of CHB.
Prof. Jinlin Hou, Director of the Center for Liver Diseases and the Institute of Hepatology at the Southern Medical University Affiliated Nanfang Hospital and the principal investigator of the study, commented, “At present, research on novel agents targeting the HBV and its host targets is in full swing, while the functional cure of CHB remains a major challenge globally. As the principal investigator of this Phase Ib study of APG-1387 in patients with CHB, I am glad that results from the study have been selected for an oral presentation at this year’s AASLD Annual Meeting. These results show that a short-term treatment with APG-1387 can stimulate immune factors with clear anti-HBV activities, and has synergistic effects in combination with sequential NA treatment. The existing safety and efficacy data suggest that combining APG-1387 with other targeted drugs is a promising therapeutic approach worth further studies.”
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “Our pioneering work in evaluating IAP inhibitors for the treatment of CHB may bring a much-needed change to the current treatment landscape. Data presented at this year’s AASLD Annual Meeting showed the preliminary efficacy and manageable safety of APG-1387, signaling the drug candidate’s therapeutic potential in CHB. Moving forward, we will press ahead with the clinical development of APG-1387 in efforts to bring a new treatment option to patients with CHB in China and around the world.”